Clinical trial NCT00005092: Chemotherapy, Radiation Therapy, and Peripheral Stem Cell Transplantation in Treating Patients With Hematologic Cancer
Official title: A Phase I Study of Photochemically Treated Donor T-Cell Supplements in HLA Haplotype Mismatched Hematopoietic Stem Cell Transplantation
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Leukemia
Lymphoma
Multiple Myeloma and Plasma Cell Neoplasm
Myelodysplastic Syndromes
Keywords: stage III adult Hodgkin lymphoma
stage IV adult Hodgkin lymphoma
recurrent childhood acute lymphoblastic leukemia
recurrent adult Hodgkin lymphoma
stage III cutaneous T-cell non-Hodgkin lymphoma
stage IV cutaneous T-cell non-Hodgkin lymphoma
recurrent cutaneous T-cell non-Hodgkin lymphoma
refractory multiple myeloma
stage III multiple myeloma
stage III childhood lymphoblastic lymphoma
stage IV childhood lymphoblastic lymphoma
recurrent childhood lymphoblastic lymphoma
stage III chronic lymphocytic leukemia
stage IV chronic lymphocytic leukemia
recurrent childhood acute myeloid leukemia
recurrent adult acute myeloid leukemia
recurrent adult acute lymphoblastic leukemia
relapsing chronic myelogenous leukemia
refractory chronic lymphocytic leukemia
childhood diffuse large cell lymphoma
childhood immunoblastic large cell lymphoma
chronic phase chronic myelogenous leukemia
accelerated phase chronic myelogenous leukemia
blastic phase chronic myelogenous leukemia
meningeal chronic myelogenous leukemia
adult acute monoblastic leukemia and acute monocytic leukemia (M5)
childhood acute monoblastic leukemia and acute monocytic leukemia (M5)
T-cell large granular lymphocyte leukemia
B-cell chronic lymphocytic leukemia
Philadelphia chromosome positive chronic myelogenous leukemia
Philadelphia chromosome negative chronic myelogenous leukemia
L1 childhood acute lymphoblastic leukemia
L2 childhood acute lymphoblastic leukemia
L3 childhood acute lymphoblastic leukemia
T-cell childhood acute lymphoblastic leukemia
B-cell childhood acute lymphoblastic leukemia
non-T, non-B childhood acute lymphoblastic leukemia
non-T, non-B, cALLa positive childhood acute lymphoblastic leukemia
non-T, non-B, cALLa negative childhood acute lymphoblastic leukemia
non-T, non-B, cALLa positive, pre-B childhood acute lymphoblastic leukemia
L1 adult acute lymphoblastic leukemia
L2 adult acute lymphoblastic leukemia
L3 adult acute lymphoblastic leukemia
T-cell adult acute lymphoblastic leukemia
B-cell adult acute lymphoblastic leukemia
non-T, non-B adult acute lymphoblastic leukemia
non-T, non-B, cALLa positive adult acute lymphoblastic leukemia
non-T, non-B, cALLa positive, pre-B adult acute lymphoblastic leukemia
non-T, non-B, cALLa negative adult acute lymphoblastic leukemia
TdT positive adult acute lymphoblastic leukemia
TdT negative adult acute lymphoblastic leukemia
TdT negative childhood acute lymphoblastic leukemia
TdT positive childhood acute lymphoblastic leukemia
adult acute erythroid leukemia (M6)
adult acute myeloblastic leukemia without maturation (M1)
adult acute myeloblastic leukemia with maturation (M2)
adult acute promyelocytic leukemia (M3)
adult acute myelomonocytic leukemia (M4)
adult acute monoblastic leukemia (M5a)
adult acute eosinophilic leukemia
adult acute basophilic leukemia
adult acute megakaryoblastic leukemia (M7)
childhood acute myeloblastic leukemia without maturation (M1)
childhood acute myeloblastic leukemia with maturation (M2)
childhood acute promyelocytic leukemia (M3)
childhood acute myelomonocytic leukemia (M4)
childhood acute monoblastic leukemia (M5a)
childhood acute monocytic leukemia (M5b)
childhood acute erythroleukemia (M6)
childhood acute eosinophilic leukemia
childhood acute basophilic leukemia
childhood acute megakaryocytic leukemia (M7)
untreated hairy cell leukemia
chronic myelomonocytic leukemia
acute undifferentiated leukemia
stage III grade 2 follicular lymphoma
stage III grade 3 follicular lymphoma
stage III adult diffuse small cleaved cell lymphoma
stage III adult diffuse mixed cell lymphoma
stage III adult diffuse large cell lymphoma
stage III adult immunoblastic large cell lymphoma
stage III adult lymphoblastic lymphoma
stage III adult Burkitt lymphoma
stage IV grade 2 follicular lymphoma
stage IV grade 3 follicular lymphoma
stage IV adult diffuse small cleaved cell lymphoma
stage IV adult diffuse mixed cell lymphoma
stage IV adult diffuse large cell lymphoma
stage IV adult immunoblastic large cell lymphoma
stage IV adult lymphoblastic lymphoma
recurrent grade 2 follicular lymphoma
recurrent grade 3 follicular lymphoma
recurrent adult diffuse small cleaved cell lymphoma
recurrent adult diffuse mixed cell lymphoma
recurrent adult diffuse large cell lymphoma
recurrent adult immunoblastic large cell lymphoma
recurrent adult lymphoblastic lymphoma
stage III adult T-cell leukemia/lymphoma
stage IV adult T-cell leukemia/lymphoma
recurrent adult T-cell leukemia/lymphoma
secondary acute myeloid leukemia
de novo myelodysplastic syndromes
adult acute monocytic leukemia (M5b)
previously treated myelodysplastic syndromes
secondary myelodysplastic syndromes
prolymphocytic leukemia
adult acute minimally differentiated myeloid leukemia (M0)
childhood acute minimally differentiated myeloid leukemia (M0)
intraocular lymphoma
stage III childhood large cell lymphoma
stage IV childhood large cell lymphoma
recurrent childhood large cell lymphoma
childhood large cell lymphoma
stage III mantle cell lymphoma
stage IV mantle cell lymphoma
recurrent mantle cell lymphoma
angioimmunoblastic T-cell lymphoma
anaplastic large cell lymphoma
stage III mycosis fungoides/Sezary syndrome
stage IV mycosis fungoides/Sezary syndrome
recurrent mycosis fungoides/Sezary syndrome
childhood myelodysplastic syndromes
Lead sponsor: M.D. Anderson Cancer Center
Sponsor class: OTHER
Collaborators: name: National Cancer Institute (NCI)
First posted: 2004-04-23
Enrollment: 7
Sex: ALL
Maximum age (years): 49
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: RATIONALE: Peripheral stem cell transplantation may be able to replace immune cells that were destroyed by the chemotherapy or radiation therapy used to kill tumor cells. Sometimes the transplanted cells are rejected by the body's normal tissues. Transplanting donated cells that have been treated with psoralen may prevent this from happening.

PURPOSE: Phase I trial to study the effectiveness of chemotherapy, radiation therapy, and psoralen-treated donor cells in treating patients who are undergoing peripheral stem cell transplantation for hematologic cancer.

Detailed description: OBJECTIVES: I. Determine the maximum tolerated dose of T-cells photochemically treated with psoralen and ultraviolet A given with peripheral stem cell transplantation in patients with hematologic malignancies or bone marrow failure myelodysplastic syndrome. II. Assess the toxicity of this treatment in these patients. III. Evaluate this regimen in terms of prevention of graft versus host disease and control of malignancy in these patients.

OUTLINE: This is a dose escalation, multicenter study of T-cells photochemically treated with psoralen and ultraviolet A. Patients receive thiotepa IV over 2 hours on day 1, cyclophosphamide IV over 2 hours on days 2 and 3, and whole body radiotherapy on days 5-8. Patients undergo preserved stem cell or bone marrow allogeneic transplant plus psoralen treated T-cell allogeneic transplant on day 9. Cohorts of 3-6 patients receive escalating doses of photochemically treated T-cells until the maximum tolerated dose (MTD) is determined. The MTD is defined as the dose preceding that at which at least 2 of 3 patients experience dose limiting toxicities. Patients are followed for 100 days.

PROJECTED ACCRUAL: A maximum of 37 patients will be accrued for this study.

Eligibility criteria: DISEASE CHARACTERISTICS: Hematologic malignancy, including acute myeloid or lymphoid leukemia of any FAB subtype, not in remission with chemotherapy or requiring bone marrow transplant OR Chronic myeloid leukemia, advanced beyond first chronic phase OR Myelodysplasia, including secondary to prior chemotherapy, with: Granulocyte count less than 500/mm3 OR Platelet count less than 50,000/mm3 OR High risk cytogenetic abnormalities such as +8, -7, -5, or 11q23 OR Intermediate or high grade lymphoma without response to initial therapy or in relapse OR Multiple myeloma without response to initial therapy or in relapse OR Stage IV low grade lymphoma or chronic lymphocytic leukemia not achieving remission with 2 regimens No aplastic anemia Related haploidentical donor (1-3 HLA-A, B, and/or DR mismatch) for collection of stem cells and whole blood T-cells required

PATIENT CHARACTERISTICS: Age: 6 months to 49 years Performance status: ECOG 0-2 Life expectancy: Greater than 12 weeks Hematopoietic: See Disease Characteristics Hepatic: Bilirubin less than 1.5 mg/dL SGPT less than 3 times upper limit of normal Renal: Creatinine less than 1.5 mg/dL Cardiovascular: Left ventricular ejection fraction at least 45% No symptoms or active treatment of left ventricular failure Pulmonary: Corrected DLCO at least 50% Other: No acute viral, bacterial, or fungal infection No prior transfusion associated graft versus host disease No other medical condition that would preclude study Not pregnant or nursing Negative pregnancy test Fertile patients must use effective contraception

PRIOR CONCURRENT THERAPY: Biologic therapy: At least 3 weeks since prior immunotherapy or interferon alfa and recovered No prior autologous or allogeneic progenitor cell transplant Chemotherapy: See Disease Characteristics At least 3 weeks since prior chemotherapy and recovered Endocrine therapy: Not specified Radiotherapy: At least 3 weeks since prior radiotherapy and recovered Surgery: Not specified

Primary outcomes:
measure: Maximum Tolerated Dose (MTD) of T-cells photochemically treated with psoralen and ultraviolet A
timeFrame: 100 days
Secondary outcomes:
Other outcomes:
Locations:
city: Chicago
country: United States
facility: University of Illinois at Chicago
state: Illinois
city: Saint Louis
country: United States
facility: Washington University Barnard Cancer Center
state: Missouri
city: Houston
country: United States
facility: University of Texas - MD Anderson Cancer Center
state: Texas
Study officials:
affiliation: M.D. Anderson Cancer Center
name: James Gajewski, MD
role: STUDY_CHAIR
References: