A Phase I Study of Photochemically Treated Donor T-Cell Supplements in HLA Haplotype Mismatched Hematopoietic Stem Cell Transplantation
Phase 1
N/A
49 Years
N/A
49 Years
Not Enrolling
Both
Leukemia, Lymphoma, Multiple Myeloma and Plasma Cell Neoplasm, Myelodysplastic Syndromes
Both
Leukemia, Lymphoma, Multiple Myeloma and Plasma Cell Neoplasm, Myelodysplastic Syndromes
Trial Information
A Phase I Study of Photochemically Treated Donor T-Cell Supplements in HLA Haplotype Mismatched Hematopoietic Stem Cell Transplantation
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.
Inclusion 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
Type of Study:
Interventional
Study Design:
Allocation: Non-Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Outcome Measure:
Maximum Tolerated Dose (MTD) of T-cells photochemically treated with psoralen and ultraviolet A
Outcome Description:
MTD defined as dose preceding that at which at least 2 of 3 patients experience dose limiting toxicities. Patients followed for 100 days.
Outcome Time Frame:
100 days
Safety Issue:
Yes
Principal Investigator
James Gajewski, MD
Investigator Role:
Study Chair
Investigator Affiliation:
M.D. Anderson Cancer Center
Authority:
United States: Institutional Review Board
Study ID:
DM98-283
NCT ID:
NCT00005092
Start Date:
March 1999
Completion Date:
August 2002
Related Keywords:
- Leukemia
- Lymphoma
- Multiple Myeloma and Plasma Cell Neoplasm
- Myelodysplastic Syndromes
- 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
- Neoplasms
- Leukemia
- Lymphoma
- Lymphoma, Non-Hodgkin
- Multiple Myeloma
- Neoplasms, Plasma Cell
- Plasmacytoma
- Myelodysplastic Syndromes
- Preleukemia
- Lymphoma, Large-Cell, Immunoblastic
Name | Location |
|---|---|
| University of Texas - MD Anderson Cancer Center | Houston, Texas 77030-4009 |
| University of Illinois at Chicago | Chicago, Illinois 60612 |
| Washington University Barnard Cancer Center | Saint Louis, Missouri 63110 |
