Treatment of T-cell lymphoma using 10-propargyl-10-deazaaminopterin

1. A method for treatment of peripheral T cell lymphoma excluding mycosis fungoides comprising administering to a human having a peripheral T cell lymphoma other than mycosis fungoides a composition comprising a therapeutically effective amount of 10-propargyl-10-deazaaminopterin.

2. A method for treatment of peripheral T cell lymphoma excluding mycosis fungoides comprising administering to a human having a peripheral T cell lymphoma other than mycosis fungoides a composition comprising a therapeutically effective amount of 10-propargyl-10-deazaaminopterin, wherein the composition is formulated with 10-propargyl-10-deazaaminopterin substantially free of 10-deazaaminopterin.

3. The method of claim 1 , wherein the 10-propargyl-10-deazaaminopterin is administered in an amount of from 30 to 275 mg/m 2 per dose.

4. The method of claim 3 , wherein the 10-propargyl-10-deazaaminopterin is administered weekly.

5. The method of claim 4 , wherein the 10-propargyl-10-deazaaminopterin is administered in an amount of 30 mg/m 2 per dose.

6. The method of claim 4 , wherein the 10-propargyl-10-deazaaminopterin is administered in an amount of from 30 to 150 mg/m 2 per dose.

7. The method of claim 1 , wherein the 10-propargyl-10-deazaaminopterin is administered biweekly.

8. The method of claim 7 , wherein the 10-propargyl-10-deazaaminopterin is administered in an amount of from 135 to 275 mg/m 2 per dose.

9. The method of claim 2 , wherein the 10-propargyl-10-deazaaminopterin is administered in an amount of from 30 to 275 mg/m 2 per dose.

10. The method of claim 2 , wherein the 10-propargyl-10-deazaaminopterin is administered weekly.

11. The method of claim 10 , wherein the 10-propargyl-10-deazaaminopterin is administered in an amount of 30 mg/m 2 per dose.

12. The method of claim 10 , wherein the 10-propargyl-10-deazaaminopterin is administered in an amount of from 30 to 150 mg/m 2 per dose.

13. The method of claim 2 , wherein the 10-propargyl-10-deazaaminopterin is administered biweekly.

14. The method of claim 13 , wherein the 10-propargyl-10-deazaaminopterin is administered in an amount of from 135 to 275 mg/m 2 per dose.

15. The method of claim 1 , wherein the peripheral T cell lymphoma is an a Human T-lymphotropic virus (HTLV) Associated T-cell Lymphoma/leukemia.

16. The method of claim 15 , wherein the composition is formulated with 10-propargyl-10-deazaaminopterin substantially free of 10-deazaaminopterin.

17. The method of claim 16 , wherein the 10-propargyl-10-deazaaminopterin is administered in an amount of from 30 to 275 mg/m 2 per dose.

18. The method of claim 16 , wherein the 10-propargyl-10-deazaaminopterin is administered weekly.

19. The method of claim 18 , wherein the 10-propargyl-10-deazaaminopterin is administered in an amount of 30 mg/m 2 per dose.

20. The method of claim 18 , wherein the 10-propargyl-10-deazaaminopterin is administered in an amount of from 30 to 150 mg/m 2 per dose.

21. The method of claim 16 , wherein the 10-propargyl-10-deazaaminopterin is administered biweekly.

22. The method of claim 21 , wherein the 10-propargyl-10-deazaaminopterin is administered in an amount of from 135 to 275 mg/m 2 per dose.

23. The method of claim 1 , wherein the peripheral T cell lymphoma is a subcutaneous Panniculitic T-cell Lymphoma.

24. The method of claim 23 , wherein the composition is formulated with 10-propargyl-10-deazaaminopterin substantially free of 10-deazaaminopterin.

25. The method of claim 24 , wherein the 10-propargyl-10-deazaaminopterin is administered in an amount of from 30 to 275 mg/m 2 per dose.

26. The method of claim 24 , wherein the 10-propargyl-10-deazaaminopterin is administered weekly.

27. The method of claim 26 , wherein the 10-propargyl-10-deazaaminopterin is administered in an amount of 30 mg/m 2 per dose.

28. The method of claim 26 , wherein the 10-propargyl-10-deazaaminopterin is administered in an amount of from 30 to 150 mg/m 2 per dose.

29. The method of claim 24 , wherein the 10-propargyl-10-deazaaminopterin is administered biweekly.

30. The method of claim 29 , wherein the 10-propargyl-10-deazaaminopterin is administered in an amount from 135 to 275 mg/m 2 per dose.

31. The method of claim 1 , wherein the peripheral T cell lymphoma is selected from: T cell prolymphocytic leukemia; T-cell granular lymphocytic leukemia; aggressive NK-cell leukemia; cutaneous T cell lymphoma excluding mycosis fungoides; anaplastic large cell lymphoma, T cell type; enteropathy-type T cell lymphoma; Adult T-cell leukemia/lymphoma; angioimmunoblastic T cell lymphoma; subcutaneous panniculitic T cell lymphoma; and peripheral T cell lymphomas that initially involve a lymph node paracortex and never grow into a true follicular pattern.

32. The method of claim 31 , wherein the composition is formulated with 10-propargyl-10-deazaaminopterin substantially free of 10-deazaaminopterin.

33. The method of claim 32 , wherein the 10-propargyl-10-deazaaminopterin is administered in an amount of from 30 to 275 mg/m 2 per dose.

34. The method of claim 32 , wherein the 10-propargyl-10-deazaaminopterin is administered weekly.

35. The method of claim 34 , wherein the 10-propargyl-10-deazaaminopterin is administered in an amount of 30 mg/m 2 per dose.

36. The method of claim 34 , wherein the 10-propargyl-10-deazaaminopterin is administered in an amount of from 30 to 150 mg/m 2 per dose.

37. The method of claim 32 , wherein the 10-propargyl-10-deazaaminopterin is administered biweekly.

38. The method of claim 37 , wherein the 10-propargyl-10-deazaaminopterin is administered in an amount of from 135 to 275 mg/m 2 per dose.

39. The method of claim 1 , wherein the human treated has relapsed or refractory peripheral T cell lymphoma.

40. The method of claim 39 , wherein the 10-propargyl-10-deazaaminopterin is administered in an amount of from 30 to 275 mg/m 2 per dose.

41. The method of claim 39 , wherein the 10-propargyl-10-deazaaminopterin is administered weekly.

42. The method of claim 41 , wherein the 10-propargyl-10-deazaaminopterin is administered in an amount of 30 mg/m 2 per dose.

43. The method of claim 41 , wherein the 10-propargyl-10-deazaaminopterin is administered in an amount of from 30 to 150 mg/m 2 per dose.

44. The method of claim 39 , wherein the 10-propargyl-10-deazaaminopterin is administered biweekly.

45. The method of claim 44 , wherein the 10-propargyl-10-deazaaminopterin is administered in an amount of from 135 to 275 mg/m 2 per dose.

46. The method of claim 39 , wherein the 10-propargyl-10-deazaaminopterin is administered in one or more cycles, each cycle comprising administration once weekly for six weeks in an amount of from 30 to 150 mg/m 2 per dose followed by a one week rest.

47. The method of claim 46 , wherein the 10-propargyl-10-deazaaminopterin is administered in an amount of 30 mg/m 2 per dose.

48. The method of claim 39 , wherein the composition is formulated with 10-propargyl-10-deazaaminopterin substantially free of 10-deazaaminopterin.

49. The method of claim 48 , wherein the 10-propargyl-10-deazaaminopterin is administered in an amount of from 30 to 275 mg/m 2 per dose.

50. The method of claim 48 , wherein the 10-propargyl-10-deazaaminopterin is administered weekly.

51. The method of claim 50 , wherein the 10-propargyl-10-deazaaminopterin is administered in an amount of 30 mg/m 2 per dose.

52. The method of claim 50 , wherein the 10-propargyl-10-deazaaminopterin is administered in an amount of from 30 to 150 mg/m 2 per dose.

53. The method of claim 48 , wherein the 10-propargyl-10-deazaaminopterin is administered biweekly.

54. The method of claim 53 , wherein the 10-propargyl-10-deazaaminopterin is administered in an amount of from 135 to 275 mg/m 2 per dose.

55. The method of claim 2 , wherein the 10-propargyl-10-deazaaminopterin is administered in one or more seven-week cycles, each cycle comprising administration once weekly for six weeks in an amount of from 30 to 150 mg/m 2 per dose followed by a one week rest.

56. The method of claim 55 , wherein the 10-propargyl-10-deazaaminopterin is administered in an amount of 30 mg/m 2 per dose.

57. The method of claim 32 , wherein the 10-propargyl-10-deazaaminopterin is administered in one or more seven-week cycles, each cycle comprising administration once weekly for six weeks in an amount of from 30 to 150 mg/m 2 per dose followed by a one week rest.

58. The method of claim 57 , wherein the 10-propargyl-10-deazaaminopterin is administered in an amount of 30 mg/m 2 per dose.

59. The method of claim 48 , wherein the 10-propargyl-10-deazaaminopterin is administered in one or more seven-week cycles, each cycle comprising administration once weekly for six weeks in an amount of from 30 to 150 mg/m 2 per dose followed by a one week rest.

60. The method of claim 59 , wherein the 10-propargyl-10-deazaaminopterin is administered in an amount of 30 mg/m 2 per dose.

61. The method of claim 55 , further comprising supplementation with folic acid and vitamin B 12 .

62. The method of claim 57 , further comprising supplementation with folic acid and vitamin B 12 .

63. The method of claim 59 , further comprising supplementation with folic acid and vitamin B 12 .

64. The method of claim 31 , wherein the peripheral T cell lymphoma is Sézary syndrome.

65. The method of claim 31 , wherein the peripheral T cell lymphoma is Adult T cell leukemia/lymphoma associated with Human T-lymphotropic virus-1 (HTLV-1).

66. The method of claim 31 , wherein the composition is administered as an oral liquid or as an injectable solution.

67. The method of claim 1 , wherein the composition is administered as an oral liquid or as an injectable solution.

68. The method of claim 2 , wherein the composition is administered as an oral liquid or as an injectable solution.

69. A method for treatment of peripheral T cell lymphoma excluding mycosis fungoides comprising administering to a human having a peripheral T cell lymphoma other than mycosis fungoides a composition comprising a therapeutically effective amount of a salt form of 10-propargyl- 10-deazaaminopterin.

70. The method of claim 69 , wherein the 10-propargyl-10-deazaaminopterin is administered in an amount of from 30 to 275 mg/m 2 per dose.

71. The method of claim 69 , wherein the 10-propargyl-10-deazaaminopterin is administered weekly.

72. The method of claim 71 , wherein the 10-propargyl-10-deazaaminopterin is administered in an amount of 30 mg/m 2 per dose.

73. The method of claim 71 , wherein the 10-propargyl-10-deazaaminopterin is administered in an amount of from 30 to 150 mg/m 2 per dose.

74. The method of claim 69 , wherein the 10-propargyl-10-deazaaminopterin is administered biweekly.

75. The method of claim 74 , wherein the 10-propargyl-10-deazaaminopterin is administered in an amount of from 135 to 275 mg/m 2 per dose.

76. The method of claim 69 , wherein the peripheral T cell lymphoma is a Human T-lymphotropic virus (HTLV) Associated T-cell Lymphoma/leukemia.

77. The method of claim 76 , wherein the composition is administered as an oral liquid or injectable solution.

78. The method of claim 76 , wherein the 10-propargyl-10-deazaaminopterin is administered in an amount of from 30 to 275 mg/m 2 per dose.

79. The method of claim 76 , wherein the 10-propargyl-10-deazaaminopterin is administered weekly.

80. The method of claim 79 , wherein the 10-propargyl-10-deazaaminopterin is administered in an amount of 30 mg/m 2 per dose.

81. The method of claim 79 , wherein the 10-propargyl-10-deazaaminopterin is administered in an amount of from 30 to 150 mg/m 2 per dose.

82. The method of claim 76 , wherein the 10-propargyl-10-deazaaminopterin is administered biweekly.

83. The method of claim 82 , wherein the 10-propargyl-10-deazaaminopterin is administered in an amount of from 135 to 275 mg/m 2 per dose.

84. The method of claim 69 , wherein the peripheral T cell lymphoma is a subcutaneous Panniculitic T-cell Lymphoma.

85. The method of claim 84 , wherein the composition is administered an oral liquid or as an injectable solution.

86. The method of claim 84 , wherein the 10-propargyl-10-deazaaminopterin is administered in an amount of from 30 to 275 mg/m 2 per dose.

87. The method of claim 84 , wherein the 10-propargyl-10-deazaaminopterin is administered weekly.

88. The method of claim 86 , wherein the 10-propargyl-10-deazaaminopterin is administered in an amount of 30 mg/m 2 per dose.

89. The method of claim 86 , wherein the 10-propargyl-10-deazaaminopterin is administered in an amount of from 30 to 150 mg/m 2 per dose.

90. The method of claim 84 , wherein the 10-propargyl-10-deazaaminopterin is administered biweekly.

91. The method of claim 90 , wherein the 10-propargyl-10-deazaaminopterin is administered in an amount from 135 to 275 mg/m 2 per dose.

92. The method of claim 69 , wherein the peripheral T cell lymphoma is selected from: T cell prolymphocytic leukemia; T-cell granular lymphocytic leukemia; aggressive NK-cell leukemia; cutaneous T cell lymphoma excluding mycosis fungoides; anaplastic large cell lymphoma, T cell type; enteropathy-type T cell lymphoma; Adult T-cell leukemia/lymphoma; angioimmunoblastic T cell lymphoma; subcutaneous panniculitic T cell lymphoma; and peripheral T cell lymphomas that initially involve a lymph node paracortex and never grow into a true follicular pattern.

93. The method of claim 92 , wherein the 10-propargyl-10-deazaaminopterin is administered in an amount of from 30 to 275 mg/m 2 per dose.

94. The method of claim 92 , wherein the 10-propargyl-10-deazaaminopterin is administered weekly.

95. The method of claim 94 , wherein the 10-propargyl-10-deazaaminopterin is administered in an amount of 30 mg/m 2 per dose.

96. The method of claim 94 , wherein the 10-propargyl-10-deazaaminopterin is administered in an amount of from 30 to 150 mg/m 2 per dose.

97. The method of claim 92 , wherein the 10-propargyl-10-deazaaminopterin is administered biweekly.

98. The method of claim 97 , wherein the 10-propargyl-10-deazaaminopterin is administered in an amount of from 135 to 275 mg/m 2 per dose.

99. The method of claim 92 , wherein the 10-propargyl-10-deazaaminopterin is administered in one or more seven-week cycles, each cycle comprising administration once weekly for six weeks in an amount of from 30 to 150 mg/m 2 per dose followed by a one week rest.

100. The method of claim 99 , wherein the 10-propargyl-10-deazaaminopterin is administered in an amount of 30 mg/m 2 per dose.

101. The method of claim 100 , further comprising supplementation with folic acid and vitamin B 12 .

102. The method of claim 69 , wherein the human treated has relapsed or refractory peripheral T cell lymphoma.

103. The method of claim 102 , wherein the composition is administered as an injectable solution.

104. The method of claim 102 , wherein the 10-propargyl-10-deazaaminopterin is administered in an amount of from 30 to 275 mg/m 2 per dose.

105. The method of claim 102 , wherein the 10-propargyl-10-deazaaminopterin is administered weekly.

106. The method of claim 95 , wherein the 10-propargyl-10-deazaaminopterin is administered in an amount of 30 mg/m 2 per dose.

107. The method of claim 95 , wherein the 10-propargyl-10-deazaaminopterin is administered in an amount of from 30 to 150 mg/m 2 per dose.

108. The method of claim 102 , wherein the 10-propargyl-10-deazaaminopterin is administered biweekly.

109. The method of claim 108 , wherein the 10-propargyl-10-deazaaminopterin is administered in an amount of from 135 to 275 mg/m 2 per dose.

110. The method of claim 102 , wherein the 10-propargyl-10-deazaaminopterin is administered in one or more cycles, each cycle comprising administration once weekly for six weeks in an amount of from 30 to 150 mg/m 2 per dose followed by a one week rest.

111. The method of claim 110 , wherein the 10-propargyl-10-deazaaminopterin is administered in an amount of 30 mg/m 2 per dose.

112. The method of claim 69 , wherein the peripheral T cell lymphoma is Sézary syndrome.

113. A method for treatment of peripheral T cell lymphoma excluding mycosis fungoides comprising administering to a human having a peripheral T cell lymphoma other than mycosis fungoides a composition comprising a therapeutically effective amount of 10-propargyl-10-deazaaminopterin, wherein the composition is formulated with 10-propargyl-10-deazaaminopterin in salt form substantially free of 10-deazaaminopterin.

114. The method of claim 113 , wherein the 10-propargyl-10-deazaaminopterin is administered in an amount of from 30 to 275 mg/m 2 per dose.

115. The method of claim 113 , wherein the 10-propargyl-10-deazaaminopterin is administered weekly.

116. The method of claim 115 , wherein the 10-propargyl-10-deazaaminopterin is administered in an amount of 30 mg/m 2 per dose.

117. The method of claim 115 , wherein the 10-propargyl-10-deazaaminopterin is administered in an amount of from 30 to 150 mg/m 2 per dose.

118. The method of claim 113 , wherein the 10-propargyl-10-deazaaminopterin is administered biweekly.

119. The method of claim 118 , wherein the 10-propargyl-10-deazaaminopterin is administered in an amount of from 135 to 275 mg/m 2 per dose.

120. The method of claim 113 , wherein the composition is administered as an oral liquid or as an injectable solution.

121. The method of claim 113 , wherein the peripheral T cell lymphoma is a Human T-lymphotropic virus (HTLV) Associated T-cell Lymphoma/leukemia.

122. The method of claim 121 , wherein the composition is administered as an oral liquid or injectable solution.

123. The method of claim 121 , wherein the 10-propargyl-10-deazaaminopterin is administered in an amount of from 30 to 275 mg/m 2 per dose.

124. The method of claim 121 , wherein the 10-propargyl-10-deazaaminopterin is administered weekly.

125. The method of claim 124 , wherein the 10-propargyl-10-deazaaminopterin is administered in an amount of 30 mg/m 2 per dose.

126. The method of claim 124 , wherein the 10-propargyl-10-deazaaminopterin is administered in an amount of from 30 to 150 mg/m 2 per dose.

127. The method of claim 121 , wherein the 10-propargyl-10-deazaaminopterin is administered biweekly.

128. The method of claim 126 , wherein the 10-propargyl-10-deazaaminopterin is administered in an amount of from 135 to 275 mg/m 2 per dose.

129. The method of claim 113 , wherein the peripheral T cell lymphoma is a subcutaneous Panniculitic T-cell Lymphoma.

130. The method of claim 129 , wherein the composition is administered an oral liquid or as an injectable solution.

131. The method of claim 129 , wherein the 10-propargyl-10-deazaaminopterin is administered in an amount of from 30 to 275 mg/m 2 per dose.

132. The method of claim 131 , wherein the 10-propargyl-10-deazaaminopterin is administered weekly.

133. The method of claim 132 , wherein the 10-propargyl-10-deazaaminopterin is administered in an amount of 30 mg/m 2 per dose.

134. The method of claim 132 , wherein the 10-propargyl-10-deazaaminopterin is administered in an amount of from 30 to 150 mg/m 2 per dose.

135. The method of claim 131 , wherein the 10-propargyl-10-deazaaminopterin is administered biweekly.

136. The method of claim 135 , wherein the 10-propargyl-10-deazaaminopterin is administered in an amount from 135 to 275 mg/m 2 per dose.

137. The method of claim 113 , wherein the peripheral T cell lymphoma is selected from: T cell prolymphocytic leukemia; T-cell granular lymphocytic leukemia; aggressive NK-cell leukemia; cutaneous T cell lymphoma excluding mycosis fungoides; anaplastic large cell lymphoma, T cell type; enteropathy-type T cell lymphoma; Adult T-cell leukemia/lymphoma; angioimmunoblastic T cell lymphoma; subcutaneous panniculitic T cell lymphoma; and peripheral T cell lymphomas that initially involve a lymph node paracortex and never grow into a true follicular pattern.

138. The method of claim 137 , wherein the 10-propargyl-10-deazaaminopterin is administered in an amount of from 30 to 275 mg/m 2 per dose.

139. The method of claim 137 , wherein the 10-propargyl-10-deazaaminopterin is administered weekly.

140. The method of claim 139 , wherein the 10-propargyl-10-deazaaminopterin is administered in an amount of 30 mg/m 2 per dose.

141. The method of claim 139 , wherein the 10-propargyl-10-deazaaminopterin is administered in an amount of from 30 to 150 mg/m 2 per dose.

142. The method of claim 137 , wherein the 10-propargyl-10-deazaaminopterin is administered biweekly.

143. The method of claim 142 , wherein the 10-propargyl-10-deazaaminopterin is administered in an amount of from 135 to 275 mg/m 2 per dose.

144. The method of claim 137 , wherein the 10-propargyl-10-deazaaminopterin is administered in one or more seven-week cycles, each cycle comprising administration once weekly for six weeks in an amount of from 30 to 150 mg/m 2 per dose followed by a one week rest.

145. The method of claim 144 , wherein the 10-propargyl-10-deazaaminopterin is administered in an amount of 30 mg/m 2 per dose.

146. The method of claim 137 , further comprising supplementation with folic acid and vitamin B 12 .

147. The method of claim 113 , wherein the human treated has relapsed or refractory peripheral T cell lymphoma.

148. The method of claim 147 , wherein the composition is administered as an injectable solution.

149. The method of claim 147 , wherein the 10-propargyl-10-deazaaminopterin is administered in an amount of from 30 to 275 mg/m 2 per dose.

150. The method of claim 147 , wherein the 10-propargyl-10-deazaaminopterin is administered weekly.

151. The method of claim 150 , wherein the 10-propargyl-10-deazaaminopterin is administered in an amount of 30 mg/m 2 per dose.

152. The method of claim 150 , wherein the 10-propargyl-10-deazaaminopterin is administered in an amount of from 30 to 150 mg/m 2 per dose.

153. The method of claim 147 , wherein the 10-propargyl-10-deazaaminopterin is administered biweekly.

154. The method of claim 153 , wherein the 10-propargyl-10-deazaaminopterin is administered in an amount of from 135 to 275 mg/m 2 per dose.

155. The method of claim 147 , wherein the 10-propargyl-10-deazaaminopterin is administered in one or more cycles, each cycle comprising administration once weekly for six weeks in an amount of from 30 to 150 mg/m 2 per dose followed by a one week rest.

156. The method of claim 155 , wherein the 10-propargyl-10-deazaaminopterin is administered in an amount of 30 mg/m 2 per dose.

157. The method of claim 113 , wherein the peripheral T cell lymphoma is Sézary syndrome.

158. The method of claim 113 , wherein the peripheral T cell lymphoma is Adult T cell leukemia/lymphoma associated with Human T-lymphotropic virus-1 (HTLV-1).

159. The method of claim 113 , wherein the 10-propargyl-10-deazaaminopterin is administered in one or more seven-week cycles, each cycle comprising administration once weekly for six weeks in an amount of from 30 to 150 mg/m 2 per dose followed by a one week rest.

160. The method of claim 159 , wherein the 10-propargyl-10-deazaaminopterin is administered in an amount of 30 mg/m 2 per dose.

161. The method of claim 113 , further comprising supplementation with folic acid and vitamin B 12 .